- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT02939079
Evaluating of the Effect of Fingolimod With Fish Oil on Relapsing-Remitting Multiple Sclerosis Patients
Evaluating the Effect of Fingolimod With Fish Oil Compared to Fingolimod With Placebo on Tumor Necrosis Factor-α , Interleukin1b , Interleukin6, and Interferon-gamma in Patients With Relapsing-Remitting Multiple Sclerosis
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
Multiple Sclerosis (MS) is a chronic autoimmune disease characterized by inflammatory demyelinative lesions in central nervous system. Relapsing-Remitting MS is the most common form of the disease observed in 85% of patients. This form presents with acute or sub-acute onset of neurological symptoms and patients may fully or partially recover and relapses may occur from time to time.
Regarding MS pathogenesis, the findings suggest the role of environmental factors in triggering the innate immune system and activating T cells and the onset of a chronic inflammatory response against myelin antigens in the central nervous system in people who are genetically prone to the disease. Among immune cells, T helper 17 (Th17) plays an important role in autoimmune response and are shown to be involved in clinical course of Relapsing-Remitting MS. Th17 cell differentiation is controlled by several cytokines, including interleukin-6 (IL-6), interleukin-1b (IL-1b) and interleukin-10 (IL-10). Also, IL 6 have an inhibitory effect on Th17 cell differentiation through increased production of interferon-gamma (IFN-gamma) and IL 10.
Currently, immunomodulatory drugs are considered as the first line treatment in MS. Fingolimod is the first oral immunomodulatory medication used for Relapsing-Remitting MS. It is phosphorylated by crossing the blood-brain barrier and is converted to its active metabolite, Fingolimod-P. This metabolite acts as a Sphingosine-1-phosphate receptor (S1PR1) on oligodendrocytes, microglias, astrocytes, and neurons and inhibits the entry of lymphocytes into the central nervous system. Therefore, it reduces demyelination and may also lead to remyelination.
Nutrition is known as a possible environmental factor in pathogenesis of MS. Positive clinical and biological effects of dietary supplements containing polyunsaturated fatty acids omega -3 (PUFA) in the course of autoimmune diseases such as MS have been studied. High levels of PUFA is found in fish oil which is also known as an antioxidant, anti-inflammatory and immunomodulatory agent. Several studies have evaluated the effect of fish oil as a dietary supplement in the treatment of MS however, conflicting findings are reported.
In this study, the investigators aim to evaluate the effect of Fingolimod with Fish oil compared to Fingolimod with placebo on TNF-α, IL1b, IL6, and IFN-gamma in patients with Relapsing-Remitting Multiple sclerosis.
Type d'étude
Inscription (Réel)
Phase
- Phase 2
- Phase 3
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Patients with relapsing-remitting multiple sclerosis according to McDonald's criteria (2010)
- Age between 18 and 45 years
- Expanded Disability Status Scale (EDSS) between 0-5
- History of at least one relapse during the last year
- Intolerance or serious complications when receiving interferons
- Not receiving interferons in the last two months
- Not having relapse in the last 30 days
- Negative pregnancy test
- History of varicella or varicella vaccination, or positive test for anti-varicella antibodies
- Not to take any medication or dietary complement without permission of the physician
- Filling informed consent
Exclusion Criteria:
- Having chronic and infectious diseases
- History of cardiovascular diseases
- Taking corticosteroids in the last 30 days
- Taking chemotherapy agents such as Cyclophosphamide
- Patients who have taken fingolimod before
- Patients who experience relapse during the study
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Tripler
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
---|---|
Expérimental: Fingolimod and Fish Oil
Fingolimod 0.5 mg capsule daily by mouth and Fish Oil 1 g capsule daily by mouth for one year.
|
Produced by Osveh ® Pharm Company in Iran
Autres noms:
produced by Zahravi ® Pharm Company in Iran
Autres noms:
|
Comparateur actif: Fingolimod and Placebo
Fingolimod 0.5 mg capsule daily by mouth and Placebo capsule daily by mouth for one year.
|
Produced by Osveh ® Pharm Company in Iran
Autres noms:
placebo capsules to mimic Fish Oil 1 g capsules
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Serum Level of TNF-α
Délai: Baseline
|
5 cc of venous blood is taken from patients and are kept in test tubes without ethylenediaminetetraacetic acid (EDTA).
Test tubes are kept one hour immobilized so that clotted blood and serum are separated.
Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes.
Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions.
|
Baseline
|
Serum Level of IL1b
Délai: Baseline
|
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA.
Test tubes are kept one hour immobilized so that clotted blood and serum are separated.
Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes.
Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions.
|
Baseline
|
Serum Level of IL6
Délai: Baseline
|
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA.
Test tubes are kept one hour immobilized so that clotted blood and serum are separated.
Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes.
Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions.
|
Baseline
|
Serum Level of IFN-gamma
Délai: Baseline
|
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA.
Test tubes are kept one hour immobilized so that clotted blood and serum are separated.
Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes.
Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions.
|
Baseline
|
Serum Level of TNF-α
Délai: 6 months after intervention
|
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA.
Test tubes are kept one hour immobilized so that clotted blood and serum are separated.
Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes.
Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions.
|
6 months after intervention
|
Serum Level of TNF-α
Délai: 1 year after intervention
|
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA.
Test tubes are kept one hour immobilized so that clotted blood and serum are separated.
Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes.
Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions.
|
1 year after intervention
|
Serum Level of IL1b
Délai: 6 months after intervention
|
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA.
Test tubes are kept one hour immobilized so that clotted blood and serum are separated.
Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes.
Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions.
|
6 months after intervention
|
Serum Level of IL1b
Délai: 1 year after intervention
|
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA.
Test tubes are kept one hour immobilized so that clotted blood and serum are separated.
Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes.
Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions.
|
1 year after intervention
|
Serum Level of IL6
Délai: 6 months after intervention
|
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA.
Test tubes are kept one hour immobilized so that clotted blood and serum are separated.
Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes.
Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions.
|
6 months after intervention
|
Serum Level of IL6
Délai: 1 year after intervention
|
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA.
Test tubes are kept one hour immobilized so that clotted blood and serum are separated.
Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes.
Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions.
|
1 year after intervention
|
Serum Level of IFN-gamma
Délai: 6 months after intervention
|
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA.
Test tubes are kept one hour immobilized so that clotted blood and serum are separated.
Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes.
Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions.
|
6 months after intervention
|
Serum Level of IFN-gamma
Délai: 1 year after intervention
|
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA.
Test tubes are kept one hour immobilized so that clotted blood and serum are separated.
Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes.
Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions.
|
1 year after intervention
|
Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chaise d'étude: Shaygannejad Shaygannejad, M.D., Isfahan University of Medical Sciences
Publications et liens utiles
Publications générales
- Aktas O, Kury P, Kieseier B, Hartung HP. Fingolimod is a potential novel therapy for multiple sclerosis. Nat Rev Neurol. 2010 Jul;6(7):373-82. doi: 10.1038/nrneurol.2010.76. Epub 2010 Jun 15.
- Brinkmann V, Billich A, Baumruker T, Heining P, Schmouder R, Francis G, Aradhye S, Burtin P. Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov. 2010 Nov;9(11):883-97. doi: 10.1038/nrd3248. Epub 2010 Oct 29.
- Gallai V, Sarchielli P, Trequattrini A, Franceschini M, Floridi A, Firenze C, Alberti A, Di Benedetto D, Stragliotto E. Cytokine secretion and eicosanoid production in the peripheral blood mononuclear cells of MS patients undergoing dietary supplementation with n-3 polyunsaturated fatty acids. J Neuroimmunol. 1995 Feb;56(2):143-53. doi: 10.1016/0165-5728(94)00140-j.
- Kappos L, Radue EW, O'Connor P, Polman C, Hohlfeld R, Calabresi P, Selmaj K, Agoropoulou C, Leyk M, Zhang-Auberson L, Burtin P; FREEDOMS Study Group. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010 Feb 4;362(5):387-401. doi: 10.1056/NEJMoa0909494. Epub 2010 Jan 20.
- Nordvik I, Myhr KM, Nyland H, Bjerve KS. Effect of dietary advice and n-3 supplementation in newly diagnosed MS patients. Acta Neurol Scand. 2000 Sep;102(3):143-9. doi: 10.1034/j.1600-0404.2000.102003143.x.
- Ramirez-Ramirez V, Macias-Islas MA, Ortiz GG, Pacheco-Moises F, Torres-Sanchez ED, Sorto-Gomez TE, Cruz-Ramos JA, Orozco-Avina G, Celis de la Rosa AJ. Efficacy of fish oil on serum of TNF alpha , IL-1 beta , and IL-6 oxidative stress markers in multiple sclerosis treated with interferon beta-1b. Oxid Med Cell Longev. 2013;2013:709493. doi: 10.1155/2013/709493. Epub 2013 Jun 18.
- Torkildsen O, Wergeland S, Bakke S, Beiske AG, Bjerve KS, Hovdal H, Midgard R, Lilleas F, Pedersen T, Bjornara B, Dalene F, Kleveland G, Schepel J, Olsen IC, Myhr KM. omega-3 fatty acid treatment in multiple sclerosis (OFAMS Study): a randomized, double-blind, placebo-controlled trial. Arch Neurol. 2012 Aug;69(8):1044-51. doi: 10.1001/archneurol.2012.283.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Processus pathologiques
- Maladies du système nerveux
- Maladies du système immunitaire
- Maladies auto-immunes démyélinisantes, SNC
- Maladies auto-immunes du système nerveux
- Maladies démyélinisantes
- Maladies auto-immunes
- Sclérose en plaques
- Sclérose
- Sclérose en plaques, récurrente-rémittente
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents immunosuppresseurs
- Facteurs immunologiques
- Modulateurs des récepteurs phosphate de la sphingosine 1
- Chlorhydrate de fingolimod
Autres numéros d'identification d'étude
- 293396
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Description du régime IPD
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Étudie un produit d'appareil réglementé par la FDA américaine
produit fabriqué et exporté des États-Unis.
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .
Essais cliniques sur Fingolimod
-
University Hospital, Basel, SwitzerlandNovartisComplété
-
NovartisComplétéSclérose en plaques récurrente-rémittenteCanada, Australie, Israël, Belgique, République tchèque, Finlande, France, Allemagne, Grèce, Lituanie, Pays-Bas, Pologne, Fédération Russe, Slovaquie, Afrique du Sud, Suède, Suisse, Turquie, Royaume-Uni
-
Hoffmann-La RochePPDRecrutementSclérose en plaques récurrente-rémittenteÉtats-Unis, Belgique, Canada, Espagne, Inde, Italie, Mexique, Le Portugal, Argentine, L'Autriche, Brésil, Royaume-Uni, Allemagne, Pays-Bas, Serbie, Australie, Bulgarie, France, Grèce, Hongrie, Pologne, Ukraine, Estonie, Danemark, Croatie, ... et plus
-
NovartisComplétéSclérose en plaquesGrèce, Fédération Russe, Suisse, Allemagne, Israël, Irlande, Belgique, Finlande, Royaume-Uni, Pays-Bas, Canada, Roumanie, Hongrie, Pologne, République tchèque, Australie, Estonie, France, Slovaquie, Afrique du Sud, Suède, Turquie
-
University Hospital, CaenRecrutement
-
Asofarma S.A.I. y C.Zenith Technology Corporation LimitedComplétéVolontaires en bonne santéNouvelle-Zélande
-
Alembic Pharmaceuticals Ltd.Complété
-
Novartis PharmaceuticalsComplétéSclérose en plaques récurrente-rémittenteAllemagne
-
Novartis PharmaceuticalsComplétéSclérose en plaquesColombie, Panama, Pérou, Brésil, Jordan, Malaisie, Mexique, Argentine
-
Novartis PharmaceuticalsRecrutement